1. Field of the Invention
The present invention relates to antimicrobial protection and, more particularly, to a quaternary ammonium anti-microbial finish incorporating dendrimer polymers applied as a thin film coating using a silane coupling agent, and methods of use therefore.
2. Description of the Background
The attachment and subsequent proliferation of microbes at surfaces often results in a number of undesirable health, engineering or aesthetic consequences. For example, water quality may be compromised by the establishment of biofilms in water lines and cooling systems; the attachment of bacteria to medical equipment and textiles contributes to the transmission of infections; the growth of mildew on textiles leads to odors and spoilage. Biofilms are matrix-enclosed bacterial populations adherent to surfaces or interfaces.
Consequently, there has been significant research into methods to attach anti-microbials to useful articles to provide localized, continuous antimicrobial activity at the surface, and overcome the problems associated with microbial colonization. Some antimicrobial agents that are currently used to control environmental colonization may be constrained by their mode of action, or their efficacy. For example, many antibiotics, organic compounds and biocidal metals have been successfully incorporated into engineering materials and woven into fabrics. Because many of these agents act intra-cellularly, the active agent must migrate from the matrix into the microorganism in order to be effective. This may also result in a broader environmental contamination by the active agent. Other approaches include the use of compounds that can release small quantities of chlorine. However, these systems must be periodically recharged using specific wash procedures, which is not practical for many applications. The level of cellular killing is also an important consideration. Biocides are compounds that kill microorganisms such as bacteria, viruses and molds. Many of the current approaches have limited activity against Gram negative bacteria in particular, and may thus be considered “biostats” rather than biocides. The difference is more than just semantic, but can be quantified in terms of log reductions in microbials and survivability (i.e. recovery in the presence of nutrients). Biostatic agents may merely inhibit microbial proliferation, and their limited efficacy means that a significant proportion of cells remain viable, which can then be transferred to other surroundings.
What is desirable is a localized biocidal action that does not migrate from a matrix, and which does not require regeneration. This could improve the performance and lifetime of manufactured items and provide a means to prevent cross-contamination, achieve infection control, and prevent biofilm formation.
Many of the current approaches have limited activity against Gram negative bacteria in particular, and may thus be considered biostats rather than biocides.
Quaternary ammonium compounds (QACs) are a well-known example of an antimicrobial compound and are currently widely used as disinfectants. They are surface-active, wide-spectrum antimicrobial agents in which nitrogen is surrounded by four alkyl groups forming a positively charged molecule. The antimicrobial activity of QACs is markedly improved if a large aliphatic residue is attached to the quaternary nitrogen atom. This cation forms a salt with halogens such as chlorine, bromine or iodine. The biocidal action for QACs relies on an alteration of cell permeability which results in cytolytic damage and subsequent cell death. QACs are effective against a range of microorganisms that includes bacteria, viruses, molds, fungi and yeasts.
It is well-known that dendritic polymers (“dendrimers”) can be used as thin film coatings. Dendrimers are well defined, highly branched macromolecules that emanate from a central core. First developed by chemist Donald A. Tomalia and coworkers at Dow Chemical between 1979 and 1980, dendritic architecture brings a very high number of functional groups in a compact space. Subsequent research into dendrimers has endeavored to protect surfaces from soils, stains, ice, graffiti, insects, oils, corrosion and chemical and biological contaminants. For example, R. Mezzenga et al. (Compos. Sci. Technol. (2001), 612 (5), pp. 787-795) describes the use of dendritic polymers as modifiers for epoxy resins. A growing community of researchers is exploring or developing a variety of uses for dendritic macromolecules. These include nanoscale catalysts and reaction vessels, micelle mimics, magnetic resonance imaging agents, immunodiagnostics, agents for delivering drugs or genes into cells, chemical sensors, information-processing materials, high-performance polymers, adhesives and coatings, separation media, and molecular antennae for absorbing light energy and funneling it to a central core (as occurs in photosynthetic systems).
The potential of dendrimers as hosts for other molecules was demonstrated in 1994 by E. W. (Bert) Meijer, chemistry professor at Eindhoven University of Technology in the Netherlands, and his coworkers Johan F. G. A. Jansen (then a postdoctoral associate at Eindhoven) and Ellen M. M. de Brabander-van den Berg, a chemist at DSM Research in Geleen, the Netherlands. They described a “dendritic box” about 5 nm in diameter that can trap smaller molecules in the box's internal cavities [Science, 266, 1226 (1994)].
Dendrimers have also been used to deliver antimicrobials. For example, Balogh et al. synthesized dendrimer nanocomposites, dendrimers with inorganic silver or silver ions, and tested their antibacterial properties. Balogh, L. Proc. Am. Chem. Soc. Div. Colloi. & Surf. Chem., 54. (1999). For these dendrimer nanocomposites, the dendrimer itself did not have any antibacterial property.
U.S. Pat. No. 6,440,405 to Cooper et al. issued Aug. 27, 2002, describes quaternary ammonium functionalized dendrimers suitable for controlling the growth of microorganisms. A quaternary ammonium functionalized dendrimer can be represented by Dn-(W)z wherein the chemical structure of the chemical group W of a dendrimer of Generation n, is terminated by a quaternary ammonium compound. Unlike Balogh, Cooper et al.'s quaternary ammonium functionalized dendrimers derive antibacterial properties from the dendrimer itself (the surface groups of the dendrimers were transformed into quaternary ammonium groups). The quaternary ammonium functionalized dendrimers are much more effective against Gram-negative bacteria such as E. coli than comparable amounts of quaternary ammonium salt. Chen successfully immobilized these antimicrobial dendrimers onto a polyurethane in solution (post-polymerization) to create non-leaching biocidal polymers (Chen, Z. C. Ph.D. Thesis, 2000, University of Delaware).
Unfortunately, there are many non-polyurethane surfaces that are not as well suited for solution-phase immobilization, for example glass, metal, fabrics and other substrates. It would be greatly advantageous to provide a way to covalently attach quaternary ammonium dendrimer biocides to a wide variety of substrates. Silane is a known coupling agent, but there is the potential for cross-reactions between the silane functionality and the amine groups in the backbone of polypropyleneimine (PPI) dendrimers as shown in Cooper et al. Thus, even if a silane-QAC-dendrimer could be isolated, the potential for cross-linking may result in a limited shelf life.
The present invention avoids this problem by derivatizing polyester-based hyperbranched (dendritic) polymers to attach both quaternary ammonium compounds (quats) and a hydrolysable silane moiety. The quaternary ammonium provides biocidal activity, while the silane moiety provides a means to covalently attach the biocide to a variety of substrates through hydrolysis. The result is a surface treatment that combines the demonstrated high potency of quaternary ammonium compound dendrimers and hyperbranched polymers with the well-established coupling chemistry of silane functional groups. Upon hydrolysis, ethoxysilane groups will couple to functional groups such as amines and hydroxyl groups, and covalently attach. Silane coupling agents are used as surface modifiers to improve the compatibility between glass or any other substrates having exposed hydroxyl groups, and the surrounding matrix in glass fiber composites. Adhesion between the silane modified substrate and the matrix material is greatly improved, and is reflected in superior physical properties. Thus, glass and other substrates such as cotton that have exposed hydroxyl groups, or other reactive groups including amines, can be treated with silane-QAC-hyperbranched polymers to permanently attach biocides to the surface, and make them resist growth of microorganisms, in textiles, filters, clothing, shelters etc. The present invention is an attempt to provide non-leaching biocides that do not require recharging, and that have superior biocidal activity over traditional bacteriostatic linear quat salts.